Methods of increasing collagen formation and cellular migration in intact skin

Abstract

It has been discovered that vascular endothelial growth factor (“VEGF”) promotes migration of activated (but not differentiating) keratinocytes to skin. This growth factor specifically increases migration of keratinocytes of the “wounded skin” phenotype but does not have significant effects upon differentiated keratinocytes. It also increases collagen deposition and reduces wrinkles, enhances skin quality, and increases skin thickness to normal levels in individuals where skin has thinned due to age or disorder such as diabetes. It is particularly well suited for use as cosmeceuticals when applied in purified form and in known amounts. The data presented in the examples demonstrate efficacy and specificity of VEGF in enhancing migration of normal human keratinocytes as well as formation of new granulation tissue including collagen formation. VEGF induces keratinocyte and fibroblast migration, formation of new tissue, and not only induces deposition of collagen but improves alignment of the collagen fibers. Accordingly, this growth factor is highly suitable for use as a cosmeceutical, especially for skin resurfacing and reduction in wrinkles.

We claim:  
     
       1. A method of increasing collagen formation in intact skin comprising administering topically or locally to intact skin a composition wherein the active ingredient consists of Vascular Endothelial Growth Factor (VEGF) in an effective amount to increase collagen formation in the intact skin. 
     
     
       2. The method of  claim 1  comprising administering the composition to the surface of the skin to be treated, wherein the active agent in the composition consists of VEGF in a formulation for topical application to the skin. 
     
     
       3. The method of  claim 1  comprising administering the composition by intradermal or subcutaneous injection, wherein the active agent in the composition consists of VEGF in a pharmaceutically acceptable carrier for injection. 
     
     
       4. The method of  claim 1 , wherein the composition comprises a sustained or controlled release formulation providing VEGF at the site to be treated for between one and 10 days. 
     
     
       5. The method of  claim 1  further comprising exfoliation prior to or at the time of administration of the VEGF. 
     
     
       6. The method of  claim 1 , wherein the collagen formation comprises collagen deposition. 
     
     
       7. The method of  claim 1 , wherein the composition is administered to the intact skin of a subject with wrinkled skin. 
     
     
       8. The method of  claim 1 , wherein the VEGF is administered to the skin in combination with an exfoliant or laser treatment. 
     
     
       9. The method of  claim 1 , wherein the VEGF is administered to the intact skin following or at the time of surgical removal or reshaping of the skin. 
     
     
       10. The method of  claim 1 , wherein the composition is administered to fine lines, wrinkles, age spots, or a combination thereof. 
     
     
       11. The method of  claim 1 , wherein the composition is administered to skin damaged by disease or sun. 
     
     
       12. The method of  claim 1 , wherein the composition is administered to the intact skin of a subject with diabetes. 
     
     
       13. A method of increasing migration of activated keratinocytes in intact skin comprising administering topically or locally to intact skin a composition wherein the active ingredient consists of Vascular Endothelial Growth Factor (VEGF) in an effective amount to increase migration of the activated keratinocytes in the intact skin. 
     
     
       14. The method of  claim 13  comprising administering the composition to the surface of the skin to be treated, wherein the active agent in the composition consists of VEGF in a formulation for topical application to the skin. 
     
     
       15. The method of  claim 13  comprising administering the composition by intradermal or subcutaneous injection, wherein the active agent in the composition consists of VEGF in a pharmaceutically acceptable carrier for injection. 
     
     
       16. The method of  claim 13 , wherein the composition comprises a sustained or controlled release formulation providing VEGF at the site to be treated for between one and 10 days. 
     
     
       17. The method of  claim 13 , further comprising exfoliation prior to or at the time of administration of the VEGF. 
     
     
       18. The method of  claim 13 , wherein the composition is administered to the skin of a subject with wrinkled skin. 
     
     
       19. The method of  claim 13 , wherein the VEGF is administered to the skin in combination with an exfoliant or laser treatment. 
     
     
       20. The method of  claim 13 , wherein the VEGF is administered to the intact skin following or at the time of surgical removal or reshaping of the skin. 
     
     
       21. The method of  claim 13 , wherein the composition is administered to fine lines, wrinkles, age spots, or a combination thereof. 
     
     
       22. The method of  claim 13 , wherein the composition is administered to skin damaged by disease or sun. 
     
     
       23. The method of  claim 13 , wherein the composition is administered to the intact skin of a subject with diabetes.